AC-021 Elevated progesterone at early follicular phase results in a lower ongoing pregnancy rate after IVF using gonadotrophin-releasing hormone agonist down-regulation short protocol

2006 ◽  
Vol 12 ◽  
pp. 23-24
Author(s):  
Y Tang ◽  
HM Xiao ◽  
MD Gong ◽  
G Lin ◽  
GX Lu
PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6837 ◽  
Author(s):  
Yingfen Ying ◽  
Tanchu Yang ◽  
Huina Zhang ◽  
Chang Liu ◽  
Junzhao Zhao

Background The efficiency of prolonged down-regulation caused by a full-dose of gonadotropin-releasing hormone agonist (GnRH-a) injected during different menstrual phases has not yet been researched. Our goal was to evaluate the effects of GnRH-a, which was used in different phases of the menstrual cycle in patients undergoing in vitro fertilization and embryo transfer. Methods This was a retrospective cohort study. A total of 320 patients received a prolonged pituitary down-regulated full-dose (3.75 mg) of triptorelin in the early follicular phase, and 160 patients received the same full-dose of triptorelin during the mid-luteal phase. Clinical and laboratory outcomes were compared between the two groups. Results The basic characteristics of the two groups were comparable. The mean number of retrieved oocytes, fertilized oocytes, cleavage oocytes and good quality embryos were comparable between the two groups. Although there was a higher antral follicle count, cyst formation rate, fertilization rate and cleavage rate in the follicular phase group, no statistically significant effects were seen on implantation rate (41.15% vs. 45.91%), clinical pregnancy rate (60.38% vs. 61.36%), ongoing pregnancy rate (57.74% vs. 57.58%), live birth rate (56.23% vs. 57.58%) or early abortion rate (2.64% vs. 3.79%) per fresh transfer cycle. Moreover, severe ovarian hyperstimulation syndrome rates at the early stage (1.89% vs. 2.27%) were low in both groups. Conclusions Prolonged pituitary down-regulation achieved by utilizing a full-dose of GnRH-a administrated in either phase of the menstrual cycle can have a positive effect on ongoing pregnancy rate and live-birth rate per fresh embryo transfer cycle. Ovarian cyst formation rate was higher in the follicular phase group, but this did not have any adverse impact on clinical results.


1986 ◽  
Vol 109 (2) ◽  
pp. 155-161 ◽  
Author(s):  
J. E. A. McIntosh ◽  
R. P. McIntosh

ABSTRACT Our aim was to determine whether release of LH and FSH can be controlled differentially by the characteristics of applied signals of stimulatory gonadotrophin-releasing hormone (GnRH) alone, free of the effects of steroid feedback or other influences from the whole animal. The outputs of both gonadotrophins were significantly correlated (r≈0·90; P<0·0005) when samples of freshly dispersed sheep pituitary cells were perifused in columns for 7 h with medium containing a range of concentrations of GnRH in various patterns of pulses. Hormone released in response to the second, third and fourth pulses from every column was analysed in detail. Dose–response relationships for both LH and FSH were very similar when cells were stimulated with 5–8500 pmol GnRH/1 in 5-min pulses every hour. When GnRH was delivered in pulses at a maximally stimulating level, the outputs of both hormones increased similarly with increasing inter-pulse intervals. Efficiency of stimulation (release of gonadotrophin/unit stimulatory GnRH) decreased (was desensitized) with increasing pulse duration in the same way for both hormones. Thus, varying the dose, interval and duration of GnRH pulses did not alter the proportions of LH and FSH released in the short-term from freshly dissociated cells. However, the same cell preparations released more LH relative to FSH when treated with maximally stimulating levels of GnRH for 3 h in the presence of 10% serum from a sheep in the follicular phase of its ovulatory cycle compared with charcoal-treated serum. Because there was no gonadotrophin synthesis under the conditions used in vitro these results suggest that changes in the LH/FSH ratio seen in whole animals are more likely to result from differential clearance from the circulation, ovarian feedback at the pituitary, differential synthesis in intact tissue or another hormone influencing FSH secretion, rather than from differences in the mechanism of acute release controlled by GnRH. J. Endocr. (1986) 109, 155–161


Author(s):  
Arie A Polim ◽  
Ivan R Sini ◽  
Indra NC Anwar ◽  
Aryando Pradana ◽  
Kurniawati Kurniawati ◽  
...  

Objective: To investigate the role of CC-highly purified Human Menopausal Gonadotropin (hpHMG) and Growth Hormone (GH) in mini-stimulation protocol to improve outcome in poor ovarian responders (POR). Method: All patients were given clomiphene citrate 150 mg from day 3 to day 7 of menstrual cycle followed by 150 IU hpHMG daily from day 8 until ovulation trigger. Two groups were observed where one group received GH and the other arm did not. In the GH group, 8 IU of GH were given from day 1 of stimulation until stimulation was stopped. GnRH antagonist was used to suppress ovulation. Result: Among 51 eligible women, 29 patients with GH and 22 patients without GH, no difference was observed in the number of oocytes retrieved (2.21 versus 2.64) and the number of embryos transferred (1.24 versus 1.68) in the GH group versus the group without GH, respectively. Total clinical pregnancy rate was 17.6%. No significant difference in pregnancy and ongoing pregnancy rate in both groups (17.2% versus 18.2%) and (13.8% versus 13.6%), respectively. In patients older than 40 years old, GH showed a 4-fold likelihood in producing top quality embryos (44.8% vs 13.6%, OR=3.6, p=0.05). Conclusion: CC-HMG regimen in mini-stimulation protocol is an effective option in poor responders. Additional GH in ministimulation program provided a higher number of top quality embryos in women older than 40 years old, although there were no difference in clinical or ongoing pregnancy rate. Keywords: CC-HMG, growth hormone, IVF, mini-stimulation protocol, poor ovarian responders


2008 ◽  
Vol 89 (4) ◽  
pp. 840-846 ◽  
Author(s):  
María-José Escribá ◽  
Jesús-Félix Zulategui ◽  
Aranzazu Galán ◽  
Amparo Mercader ◽  
José Remohí ◽  
...  

Author(s):  
Abha Maheshwari ◽  
Siladitya Bhattacharya ◽  
Salim Daya ◽  
Ahmed Fathy Gibreel ◽  
Charalambos S Siristatidis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Fernandez Sanchez ◽  
H Višnová ◽  
C Blockeel ◽  
A Pinborg ◽  
Y Khalaf ◽  
...  

Abstract Study question Does addition of choriogonadotropin beta (CG beta) to follitropin delta increase the number of good-quality blastocysts following ovarian stimulation in a long GnRH agonist protocol? Summary answer At the doses investigated, the addition of CG beta reduced the number of intermediate follicles and decreased the number of oocytes and blastocysts. What is known already CG beta is a new recombinant hCG (rhCG) molecule expressed by a human cell line (PER.C6â) with a different glycosylation profile compared to urinary hCG or rhCG derived from a Chinese Hamster Ovary (CHO) cell-line. In the first-in-human trial, the CG beta pharmacokinetics were similar between men and women. In women, the area under the curve (AUC) and the peak serum concentration (Cmax) increased dose proportionally following single and multiple daily doses. In men, a single dose of CG beta provided higher exposure with a longer half-life and proportionately higher testosterone production than rhCG derived from a CHO cell line. Study design, size, duration Placebo-controlled, double-blind, randomised trial (RAINBOW) to explore the efficacy and safety of CG beta as add-on treatment to follitropin delta in women undergoing COS in a long GnRH agonist protocol. The primary endpoint was the number of good-quality blastocysts (grade 3 BB or higher, Gardner and Schoolcraft, 1999). Subjects were randomised to receive either placebo or 1, 2, 4, 8, or 12 µg CG beta added to the daily individualised follitropin delta dose during COS. Participants/materials, setting, methods In total 619 women (30-42 years) with AMH levels between 5 and 35 pmol/L were randomized in equal proportions to the six treatment groups. All subjects were treated with an individualised dose of follitropin delta determined based on AMH (Elecsys AMH Plus Immunoassay) and body weight. Triggering was performed when 3 follicles were ≥17 mm but no more than 25 follicles ≥12 mm were reached Main results and the role of chance The incidence of cycle cancellation (range 0%-2.9%), total follitropin delta dose (mean 112 µg) and duration of stimulation (mean 10 days) were similar across the groups. A reduced number of intermediate follicles (12 to 17 mm) and fewer oocytes (mean range 9.7 to 11.2) were observed for all doses of CG beta compared to the follitropin delta only group (mean 12.5). The mean number of goodquality blastocysts was 3.3 in the follitropin delta group and ranged between 2.1 and 3.0 across the CG beta groups. The incidence of transfer cancellation was higher in the 4, 8 and 12 µg group, mostly as no blastocyst was available for transfer. In the group receiving only follitropin delta, the ongoing pregnancy rate (10-11 weeks after transfer) was high i.e. 43% per started cycle vs 28-39% in CG beta groups and 49% per transfer vs 38-50% in the CG beta groups. In line with the number of collected oocytes, the OHSS incidence was overall lower following follitropin delta with CG beta than following follitropin delta only treatment. Regardless of the dose, CG beta was safe and well-tolerated with low risk of immunogenicity. Limitations, reasons for caution The effect of the unique glycosylation of CG beta and the associated potency implications in women were not known prior to this trial. Further studies will be needed to evaluate potentially lower doses of CG beta for this and/or different indications. Wider implications of the findings The high ongoing pregnancy rate in the follitropin delta group supports the use of individualised follitropin delta dosing in a long GnRH agonist protocol. The differential potency of CG beta may have impaired the growth of intermediate follicles with the investigated doses without affecting the ongoing pregnancy rates per transfer. Trial registration number NCT03564509


2020 ◽  
Vol 2020 (1) ◽  
Author(s):  
N A Danhof ◽  
R van Eekelen ◽  
S Repping ◽  
B W J Mol ◽  
F van der Veen ◽  
...  

Abstract STUDY QUESTION What is, in couples with unexplained subfertility undergoing IUI, the impact of gonadotrophins compared to clomiphene citrate (CC) on endometrial thickness (EMT) in relation to ongoing pregnancy? SUMMARY ANSWER In women with unexplained subfertility undergoing IUI with ovarian stimulation, gonadotrophins lead to a thicker endometrium compared to CC, but this does not affect ongoing pregnancy rates. WHAT IS KNOWN ALREADY A systematic review and meta-analysis among couples with unexplained subfertility undergoing IUI with ovarian stimulation showed that women who conceived had, on average, a thicker endometrium than women who did not conceive, but this evidence is not robust due to a high level of heterogeneity. There was insufficient data to draw any conclusions on EMT and the effect on pregnancy outcomes. STUDY DESIGN, SIZE, DURATION We performed a secondary analysis of a multicentre randomized controlled superiority trial in couples with unexplained subfertility undergoing IUI with adherence to strict cancellation criteria. In total, 738 couples recruited between July 2013 and March 2016 were allocated to ovarian stimulation with gonadotrophins (n = 369) or with CC (n = 369) for a maximum of four IUI cycles. According to local protocol, recombinant FSH, urinary FSH or hMG was used. Natural conceptions and cancelled cycles were removed from this secondary analysis, as they do not provide any information on pregnancy in relation to stimulation after IUI. Ongoing pregnancy was defined as a positive heartbeat at or beyond 12 weeks of gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS We first determined the difference in EMT between women randomized to gonadotrophins (75 IU) and CC (100 mg) over all cycles using a linear mixed model. We then investigated the association between EMT and ongoing pregnancy after IUI using a logistic regression model, adjusted for the allocated drug, number of dominant follicles, female age, BMI, duration of subfertility, primary or secondary subfertility, referral status, smoking status, cycle number and total motile sperm count. To conclude, we investigated the association between EMT and ongoing pregnancy by logistic regression separately in women allocated to gonadotrophins and in women allocated to CC. MAIN RESULTS AND THE ROLE OF CHANCE A total of 666 couples underwent 1968 IUI cycles. Of these, 330 couples were allocated to gonadotrophins, of which 85 conceived leading to ongoing pregnancy (rate per cycle 8.9%) and 336 couples were allocated to CC, of which 71 conceived leading to ongoing pregnancy (rate per cycle 7.0%) (relative risk (RR) 1.22, 95% CI 0.92 to 1.61). The mean EMT was 8.9 mm (SD 2.1) in women treated with gonadotrophins and 7.5 mm (SD 2.1) in women treated with CC (adjusted mean difference 1.4 mm; 95% CI: 1.1–1.7). The overall mean EMT was 8.4 mm (SD 2.2) in women that conceived leading to ongoing pregnancy and 8.2 mm (SD 2.2) in women that did not conceive (adjusted odds ratio (OR): 1.03 per 1 mm increase, 95% CI 0.95–1.12). There was no association between EMT and ongoing pregnancy in women treated with gonadotrophins or CC (OR: 1.01 per 1 mm increase, 95% CI 0.90–1.13, and 1.10 per 1 mm increase, 95% CI 0.99–1.23, respectively). LIMITATIONS, REASON FOR CAUTION Since this is a secondary analysis, the data should be interpreted prudently as secondary analyses are prone to false-positive findings or could be underpowered to show associations that the study is not primarily set up for. WIDER IMPLICATIONS OF THE FINDINGS In women with unexplained subfertility and treated with IUI, gonadotrophins lead to a significantly thicker endometrium compared to CC, but there was no evidence of a consistent association between EMT in women treated with gonadotrophins or CC and the ongoing pregnancy rate. A relatively thin endometrium after CC is therefore not a valid reason to prefer gonadotrophins as the stimulation agent in IUI for unexplained subfertility. STUDY FUNDING/COMPETING INTEREST(S) The initial trial was funded by the Netherlands Organization for Health Research and Development (ZonMw) (Health Care Efficiency Research; project number: 80-83600-98-10 192). The EudraCT number for this trial was 2013-001034-18. Prof. Dr B.W.J.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for Merck, ObsEva and Guerbet. The other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER NTR 4057


2020 ◽  
pp. 096452842095871
Author(s):  
Meaghan E Coyle ◽  
Ieva Stupans ◽  
Katherine Abdel-Nour ◽  
Hiba Ali ◽  
Michelle Kotlyarsky ◽  
...  

Objective: To evaluate the efficacy of acupuncture compared to placebo acupuncture for women undergoing in vitro fertilisation (IVF) in a systematic review and meta-analysis. Methods: A search was conducted in seven English-language biomedical databases from their inception to 3 April 2019 to identify studies evaluating acupuncture as an adjunct to IVF treatment. Randomised controlled trials (RCTs) that compared acupuncture with placebo acupuncture using a non-invasive placebo acupuncture device in women undergoing a fresh or frozen IVF cycle were eligible, as were studies that tested placebo acupuncture as the intervention. Outcomes were clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, live birth rate and adverse events. Results: Eight RCTs involving 3607 women were included. Studies were judged to be low risk for most of the risk of bias domains. Acupuncture around the time of embryo transfer was not significantly different to placebo acupuncture in terms of the clinical pregnancy rate (6 RCTs, 2473 women, risk ratio (RR) = 0.99 (95% confidence interval (CI) = 0.88, 1.11), I2 = 51%, moderate certainty evidence), ongoing pregnancy rate (4 RCTs, 1459 women, RR = 0.88 (95% CI = 0.75, 1.02), I2 = 50%, moderate certainty evidence), miscarriage rate (4 RCTs, 502 women, RR = 1.23 (95% CI = 0.89, 1.71), I2 = 30%, high certainty evidence) or live birth rate (4 RCTs, 1835 women, RR = 0.87 (95% CI = 0.75, 1.01), I2 = 0%, high certainty evidence). Outcomes with placebo acupuncture were not significantly different to usual care. Adverse events relating to acupuncture, such as discomfort and bruising, were mild to moderate. Conclusion: Acupuncture administered around the time of embryo transfer did not have a statistically significant effect on IVF outcomes compared with placebo acupuncture.


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